IN-VIVO STIMULATION BY TAMOXIFEN OF CATHEPSIN-D RNA LEVEL IN BREAST-CANCER

We have previously shown that 3 weeks of treatment with tamoxifen, of patients with primary breast carcinomas, increased cytosolic cathepsin D protein in oestrogen receptor (ER) positive tumours [Maudelonde et al., Cancer 1989, 63, 1265-1270]. In order to investigate the mechanis m of this increase and to eliminate a transient flare-up effect, we se mi-quantified cathepsin D RNA levels by in situ hybridisation in 32 br east carcinomas from patients treated with tamoxifen for 3 weeks prior to surgery and in 35 breast cancer patients receiving no tamoxifen. W e found that tamoxifen increased cathepsin D RNA level regardless of t he ER status of the tumours. In ER positive tumours, tamoxifen increas ed the cathepsin D RNA level to the same extent as cytosolic cathepsin D protein but not in ER negative tumours. The induction of cathepsin D RNA by tamoxifen in ER positive tumours was probably due to its agon ist activity, also observed in vitro in breast cancer cell lines. Thes e results suggest that the cathepsin D gene is inducible by oestrogens in ER positive breast cancer as it is in breast cancer cell lines.